The central goal of Project 1 is to identify peptide components from conserved regions of HIV-1 proteins which are capable of stimulating a specific, MHC class I-restricted cytotoxic T lymphocyte (CTL) response in man. This research builds upon the extensive experience of Project 1 scientists in identifying immunogenic peptides from viral and tumor antigens based on allele-specific binding motifs, binding affinity to class 1 molecules in vitro, and the ability to elicit primary CTL responses in human lymphocytes and HLA transgenic mice. This methodology will be applied to identifying putative CTL epitopes in internal and surface proteins of HIV-1. The initial focus of the research will be HLA- A2 peptides since this is the most frequently expressed allele in the general population. This work can be subsequently expanded to other alleles to provide broad population coverage. By creating a candidate pool of HIV-1-derived Cit peptides, Project 1 provides the essential foundation for further pep tide evaluation by Project 2 which will study peptide recognition by lymphocytes obtained from HIV-1 infected individuals. Thus, Project I contributes directly to the development of a peptide-based immunotherapeutic for AIDS which is the central focus of this Program.